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At least 541 records · Page 30Linked to original sources
PubMed1975

Clinical evaluation of eterobarb, a new anticonvulsant drug.

Two clinical investigations of a new anticonvulsant, eterobarb, N,N' dimethoxymethyl phenobarbital (DMMP), were conducted in separate geographic regions. The drug has considerable efficacy in reducing the frequency of partial seizures, with and without secondary generalization, as well as generalized tonic-clonic seizures. Sedation did not appear to be as prominent with this barbiturate as it was with phenobarbital or primidone.

Adolescent↗
PubMed1983

A design for the prospective evaluation of the efficacy and toxicity of antiepileptic drugs in adults.

The design for the comparative evaluation of the efficacy and toxicity of phenobarbital, phenytoin, primidone, and carbamazepine is outlined. A double-blind prospective study of a sufficient number of patients can determine the optimum drug to use initially for partial and generalized tonic-clonic seizures in adults. The rationale for methods defines the major parameters that should be addressed in order to determine optimum drug for longterm seizure therapy. Major problems in the function of such a project include aspects of sample size attainment, screening/recruitment, non-drug-related losses, and adjustments to the ongoing protocol. The design, with modifications, can be used to study other antiepileptic drugs and other types of seizures.

Adult↗
PubMed1986

Barbiturates reduce human cerebral glucose metabolism.

We studied the effect of barbiturates on local cerebral glucose metabolism by performing positron emission scans before and after withdrawal of phenobarbital or primidone. The postwithdrawal scan showed a significant increase (mean, 37%) in seven of eight cortical regions tested. Patients who had serial scans without a drug change showed a nonsignificant tendency for metabolic rates to go down on the second scan (mean decrease, 7%). Addition or deletion of a single drug other than barbiturate did not change metabolic rates on repeat scans. The depression in cerebral glucose metabolic rate due to phenobarbital, if confirmed, may have bearing on the adverse neuropsychological effects of the drug.

Adult↗
PubMed1986

Disability in essential tremor: effect of treatment.

We studied 18 patients with essential tremor for difficulty with handwriting, drinking, eating, fine manipulations, and embarrassment. Propranolol and primidone reduced the amplitude of both postural and kinetic tremor. Handwriting, drinking, and eating were improved with therapy, but fine manipulations and motor performance on tapping and pegboard tests were unaltered. Embarrassment remained unchanged. Essential tremor is not a benign condition; disability can be only partly reversed with drug therapy.

Aged↗
PubMed1991

Essential tremor: clinical correlates in 350 patients.

To study the demographic and clinical correlates of essential tremor (ET), we analyzed a comprehensive database of 350 patients evaluated at the Movement Disorders Clinic at Baylor College of Medicine from 1982 to 1989. The age at onset of tremor showed bimodal distribution for both male and female patients, with peaks in 2nd and 6th decades. ET appeared most frequently in hands, followed by head, voice, tongue, leg, and trunk. Half of the patients (47%) had associated dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. At least one 1st-degree relative of 62.5% of ET patients reported tremor. Alcohol relieved tremor in 2/3 of ET patients. Sixty-eight percent of patients who had adequate follow-up improved with propranolol, and 72% with primidone. There was no significant difference in various clinical variables between the 219 patients with familial ET and 131 with sporadic ET. Patients with early-onset ET were more likely to have hand involvement and associated dystonia than patients with late-onset ET. Dystonia was more frequently associated with mild ET than with severe ET. Patients with low-frequency tremor were older and had more head but less hand involvement than patients with high-frequency tremor. The lack of relevant differences between ET subgroups suggests that, despite variable expression, ET represents a single disease entity.

Adult↗
PubMed1976

An improved UV-spectrophotometric method for routine barbiturate monitoring.

A simple, rapid, quantitative, low-cost UV-differential spectrophotometric method for the routine monitoring of phenobarbital in serum and cerebrospinal fluid is described. This method can also be used for monitoring methylphenobarbital (Phemiton) and primidone (Mysoline), since the major active metabolite of both drugs is phenobarbital. The basis for our procedure is Goldbaum's method (Anal. Chem., 24, 1604 (1952)). This method was improved with several modifications including a single extraction technique with dichloroethane, which has produced a very simple but still accurate method. The whole analysis takes less than 20 minutes. This procedure is accurate in the range from 1-100 mg/1 of phenobarbital in serum or cerebrospinal fluid.

Humans↗
PubMed1981

Monitoring of therapeutic serum concentrations of antiepileptic drugs by a newly developed gas chromatographic procedure and enzyme immunoassay (EMIT): a comparative study.

A gas chromatographic procedure for the simultaneous determination of carbamazepine, phenobarbital and phenytoin using SP 2510 DA as stationary phase is presented. The antiepileptic drugs are determined simultaneously without derivatisation under isothermal conditions by a flame ionisation detector. The gas chromatographic procedure can be easily mechanized. The coefficient of variation for the precision from day to day is 8.9% for carbamazepine, 7.0% for phenobarbital and 4.3% for phenytoin as calculated from single determinations. The deviations from the target value of spiked pool sera range from 4.3 to 9.5%. The gas chromatographic results of this method and of determinations by Dexsil 300 for primidone and SP 1000 for ethosuximide are compared with the corresponding enzyme immunoassays (EMIT). The precision of the gas chromatographic methods is somewhat better than EMIT. When patients' sera are analysed by both procedures the results show no clinically relevant differences. It can be concluded that the different methods are interchangeable and may be selected according to practical necessities.

Anticonvulsants↗
PubMed1977

[Effect of drugs on electroclinical types of epileptic seizures in Lennox-Gastaut syndrome].

The therapeutics results with the use of different drugs (diazepam, nitrazepam, clonazepam, diphenylhydantoin, barbiturates--phenobarbital and primidone--, sodium dipropylacetate and ACTH) in twenty-nine patients with Lennox--Gastaut syndrome are carefully analysed. The effect of each drug on seizures (tonic, tonic-clonic, clonic, myoclonic or myoclonic-atonic, atonic and atypical absences) during the first month of each treatment is discussed. The "specific" use of each drug on the various forms of epileptic seizures is determined and the possibility of crisis control with reduction of the drugs dosage is verified.

Adrenocorticotropic Hormone↗
PubMed1988

Hereditary essential tremor in Buenos Aires (Argentina).

A descriptive trial of essential tremor in Buenos Aires city is proposed. It may be considered as the first one like this in Latin America. During a 15 year period, sixteen families with essential tremor diagnosis have been examined, making a total of 39 patients (20 males and 19 females). The disease was basically studied from its semiological, clinico-evolutive and therapeutical view point, following a protocol. Our results indicate -- a. The clinico-evolutive characteristics: its frequency (according to race, sex, social status, age of beginning and physiopathological type), morbidity and mortality, evolution, prognosis, triggering factors, longevity and multiparity. b. The different treatment given to our patients with discussion of their pharmacokinetic and pharmacodynamic basis and evaluation of the best responses. In this matter, it is concluded that both primidone (750 mg/daily) and/or propranolol (160-240 mg/daily) are undeniably the drugs of first choice for the treatment of this disease. A comparison of the clinico-therapeutic features of this tremor in Buenos Aires and other cities is done. The study of this syndrome in Buenos Aires does not give different results from those obtained in Europe and USA.

Argentina↗
PubMed2003

Essential tremor: diagnosis and treatment.

Essential tremor is a common movement disorder in adults that interferes with the performance of functional and social activities. Differentiation of essential tremor from other tremor syndromes is important in order to provide appropriate patient education and therapy. The mainstays of pharmacotherapy are propranolol and primidone; however, in selected patients, agents such as alcohol, benzodiazepines, botulinum toxin, and gabapentin may provide symptomatic benefits. Advances in surgical interventions, such as stereotactic thalamotomy and thalamic deep brain stimulation, offer patients an alternative treatment modality when pharmacotherapy is inadequate. A treatment algorithm is provided to guide clinicians in the management of patients with essential tremor.

Acetates↗
PubMed1996

Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.

Carbamazepine is one of the most commonly prescribed antiepileptic drugs and is also used in the treatment of trigeminal neuralgia and psychiatric disorders, particularly bipolar depression. Because of its widespread and long term use, carbamazepine is frequently prescribed in combination with other drugs, leading to the possibility of drug interactions. The most important interactions affecting carbamazepine pharmacokinetics are those resulting in induction or inhibition of its metabolism. Phenytoin, phenobarbital (phenobarbitone) and primidone accelerate the elimination of carbamazepine, probably by stimulating cytochrome P450 (CYP) 3A4, and reduce plasma carbamazepine concentrations to a clinically important extent. Inhibition of carbamazepine metabolism and elevation of plasma carbamazepine to potentially toxic concentrations can be caused by stiripentol, remacemide, acetazolamide, macrolide antibiotics, isoniazid, metronidazole, certain antidepressants, verapamil, diltiazem, cimetidine, danazol and (dextropropoxyphene) propoxyphene. In other cases, toxic symptoms may result from elevated plasma concentrations of the active metabolite carbamazepine-10,11-epoxide, due to the inhibition of epoxide hydrolase by valproic acid (sodium valproate), valpromide, valnoctamide and progabide. Carbamazepine is a potent inducer of CYP3A4 and other oxidative enzyme system in the liver, and it may also increase glucuronyltransferase activity. This results in the acceleration of the metabolism of concurrently prescribed anticonvulsants, particularly valproic acid, clonazepam, ethosuximide, lamotrigine, topiramate, tiagabine and remacemide. The metabolism of many other drugs such as tricyclic antidepressants, antipsychotics, steroid oral contraceptives, glucocorticoids, oral anticoagulants, cyclosporin, theophylline, chemotherapeutic agents and cardiovascular drugs can also be induced, leading to a number of clinically relevant drug interactions. Interactions with carbamazepine can usually be predicted on the basis of the pharmacological properties of the combined drug, particularly with respect to its therapeutic index, site of metabolism and ability to affect specific drug metabolising isoenzymes. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential, and careful dosage adjustments based on serum drug concentration monitoring and clinical observation represent the mainstays for the minimisation of risks associated with these interactions.

Analgesics, Non-Narcotic↗
PubMed1982

Drug interactions with valproic acid.

Valproic acid undergoes drug-drug interactions with most of the commonly used anticonvulsants. Since it possesses a wide range of indications, concomitant use with other anticonvulsants, and hence interactions, are not infrequent. Many of these interactions are reciprocal and may have important therapeutic consequences. Valproate acts as a protein binding displacer and/or metabolic inhibitor with respect to a number of other anticonvulsants (phenobarbitone, primidone, phenytoin). Inhibition of metabolism would, in most instances, result in a decrease of the dose requirements of the affected drugs. Valproate is a low clearance drug primarily eliminated by metabolism. Its metabolism is highly inducible by some of the major anticonvulsants (e.g. carbamazepine, phenytoin). Valproate is also highly protein bound in plasma and thus is displaced by salicylates and free fatty acids. However, displacement alone, unlike induced metabolism, should not affect the drug's dose-response relationship.

Anticonvulsants↗
PubMed1980

Effect of anticonvulsant and antidepressant drugs on iodothyronines in serum.

Serum iodothyronine concentrations were measured in patients on long-term therapy with one or two anticonvulsant drugs. Diphenylhydantoin (DPH) and carbamazepine (CBZ) reduced the serum levels of thyroxine (T4) free T4 index, reverse triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2), whereas the depressant effect on the serum levels of triiodothyronine (T3) and free T3 index was small but statistically significant. In patients administered DPH and phenobarbital (PB) or CBZ and primidone (PD) the serum iodothyronine levels were also depressed, except for normal T3 and free T3 index. Patients receiving only PB or PD had normal serum levels of total and free thyroid hormones, but decreased concentrations of rT3 and 3,3'-T2. Only supratherapeutic concentrations of DPH and CBZ added in vitro to control sera significantly reduced the number of T4 and T3-binding sites, as reflected in increased T4 and T3 uptake test results. This indicates that the DPH and CBZ-induced decrease in thyroid hormone concentrations in vivo is not due to a displacement of thyroid hormones from their binding sites on serum proteins. The antidepressant drugs amitriptyline and mianserin had no effect on the thyroid hormone levels in serum.

Adult↗
PubMed1979

The use of antiepileptic drugs.

The use of antiepileptic drugs has become increasingly effective through several factors: new techniques that allow better diagnosis of the seizure disorder and its underlying cause; the development of new medications and increased knowledge of old ones; and the widespread use of antiepileptic drug-level determinations. The choice of a drug depends heavily on an accurate diagnosis of seizure type, which may determine the response to the medication. Because of better diagnostic criteria and intensive monitoring procedures, the correct seizure disorder can be more easily diagnosed and, therefore, the proper medication selected. Minimal efficacious and toxic blood concentrations have now been identified for most antiepileptic drugs. Several, including primidone, carbamazepine, methsuximide, and mephenytoin, have pharmacologically active metabolites that affect both the toxicity and efficacy of the prescribed drug and can now be measured in the plasma. The most effective use of the antiepileptic drugs depends on a combination of reliable blood level measurements, clinical observation, and knowledge of their pharmacokinetics and biotransformation.

Anticonvulsants↗
PubMed2005

Rhythmic EMG and EEG activity during voluntary movement in posthypoxic cortical action myoclonus.

A patient with posthypoxic cortical action myoclonus was studied using polygraphic EEG-EMG recording techniques and transcranial magnetic stimulation. The myoclonic jerks were not stimulus-sensitive, and were not associated with enhancement of the somatosensory evoked potential (SEP). The most prominent electrophysiological finding was that rhythmic EMG activity was produced when the patient attempted rapid voluntary movement. EEG-EMG polygraph indicated that the rhythmic EMG activity was preceded by rhythmic activity in the EEG recorded overlying the contralateral central region. The frequency of both EEG and EMG activity was the same (approximately 50 Hz). Treatment using a combination of clonazepam, carbamazepine and primidone diminished the action myoclonus, concomitant with the disappearance of the rhythmic EEG and EMG activity. In the sensorimotor cortex of the normal monkey and humans, oscillatory activity ranging between 20-50 Hz has been recorded in the local field potential. Our findings suggest that cortical hyperoscillation may produce this characteristic rhythmic EEG and EMG activity and may, in turn, be related to cortical action myoclonus.

Anticonvulsants↗
PubMed1979

[Disturbances of calcium-phosphate-metabolism by anticonvulsant drugs in relation to their serum concentration (author's transl)].

25.6% of 254 epileptic children receiving anticonvulsant drugs more than 3 years showed disturbances of Calcium-phosphate-metabolism and of ossification respectively. These disturbances are divided into 4 degrees of severity: 1. Raised alkaline phosphatase in serum alone 21 patients); 2. Metaphysial osteodystrophia (22 Pat.); 3. Generalised osteoporosis (16 Pat.) and 4. Vitamin-D sensitive rickets (6 Pat.). These abnormalities were found at most in long term-treatment with hydantoins or primidone. The measurement of serum concentration of these anticonvulsant drugs yielded significantly higher amounts in patients with abnormalities in Calcium-Phosphate-metabolism than in those patients without such ones. This result permits us to conclude that disturbances of Calcium-Phosphate-metabolism are serum-concentration-dependent side-effects of anticonvulsant drugs.

Adolescent↗
PubMed1975

Continuous phrophylcatic anticonvulsants in selected childrens with febrile convulsions.

The recurrence rate of febrile convulsions is assessed in 108 children who had had either prolonged or repeated initial fits or had both a positive family history and persisting neurological disorder. Only 7 of 40 (17%) who received continuous prophylactic phenobarbitone or primidone for at minimum of 18 months had another fit compared with 40 of 68 (59%) children who were untreated (p less than 0.0005). Indications for continuous therapy are discussed.

Child↗
PubMed1975

Flash-heater ethylation of some antiepileptic drugs.

We describe a modification of the MacGee method [Anal. Chem. 42, 421 (1970)] for rapid determination of phenytoin (diphenylhydantoin) in plasma by gas-liquid chromatography, in which an ethylaing reagent is used instead of the more common methylating reagents. With this modification, several N-methylated antiepileptic drugs can be separated from their demethylated metabolites. Our results agree well with those of Butler and Waddell [Neurology 8, 106 (1958)], who showed that in patients receiving the N-methylated compounds mephenytoin and mephobarbital, the N-demethylated products, 5-ethyl-5-phenylhydantoin and phenobarbital are found in higher concentrations in plasma than are their respective parent drugs. The method is also useful for routine determinations of phenobarbital, primidone, and phenytoin in serum, cerebrospinal fluid, or saliva.

Alkylation↗